Enhancing NA immunogenicity through novel VLP designs.

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Current influenza vaccines primarily induce hemagglutinin (HA)-reactive antibodies, with limited efficacy against neuraminidase (NA) epitopes.
• Next-generation vaccines require optimization to activate NA-reactive B cells for broader protection.

Purpose of the Study:

• To enhance the immunogenicity of the NA component in influenza vaccines.
• To investigate strategies for improving NA-reactive antibody induction while maintaining HA immunogenicity.

Main Methods:

• H1N1 virus-like particles (VLPs) were engineered using baculovirus expression systems.
• Strategies included altering the HA:NA ratio and extending the NA stalk (NA-LS) by incorporating specific amino acids.
• VLPs were purified and tested in a mouse model for immunogenicity.

Main Results:

• Modified VLPs achieved HA:NA ratios of 1:1 to 2:1, increasing NA content compared to wild-type influenza virus.
• Vaccination with H1N1 VLPs elicited robust NA-inhibitory antibody titers, even at low doses.
• Anti-HA responses were not compromised by the modifications.

Conclusions:

• The developed strategies are feasible for enhancing NA immunogenicity in influenza vaccine candidates.
• These modifications show potential for creating next-generation influenza vaccines with improved and broader protective capabilities.